The role of maternal caffeine consumption in the pathogenesis of adverse pregnancy outcomes in controversial. Several studies have found that women who consume caffeine are at increased risk of spontaneous abortion and fetal growth retardation compared to non users. However, other, equally well-done studies have found no harmful effects of caffeine consumption. In addition, several studies have reported that caffeine is harmful only among women who smoke. All previous studies of this question have relied on maternally-reported caffeine use; no studies have employed a biomarker for caffeine. This project will first validate the use of serum caffeine and its metabolites as a marker for caffeine intake, and will then study these serum markers as a risk factor for adverse pregnancy outcome. In the validation study, serum paraxanthine was determined to be an acceptable marker for caffeine intake, and the main part of this project will commence in FY 97.